The overall objectives of the proposed work are to learn more of the possible significance of K cell cytotoxicity in rheumatic diseases and related conditions. K cell cytotoxicity involves the cytotoxic action of non-immune lymphoid cells upon target cells sensitized by specific antibody. This mechanism may operate in such divergent conditions as Hashimoto's thyroiditis, transitional cell carcinoma of the bladder, rejection of kidney grafts, and immunity to microbial agents. We recently have described alteration in K cell function in the peripheral blood of patients with systemic lupus erythematosus. This information, together with data that K cell activity is modulated by immune complexes, anti-immunoglobulins, and immunosuppressive therapy, would indicate that further studies of immunologically mediated diseases are warranted. In clinical studies, we will investigate correlations of various laboratory and clinical parameters with K cell function. Additionally, in in vitro studies, we will determine the possible role of lymphocytotoxic antibodies and rheumatoid factor on the system and investigate possible implication of K cells as cytotoxic cells in dematomyositis and hemolytic anemia in systemic lupus erythematosus.